The ability to successfully interface the brain to external electronics would have enormous implications for our society, and facilitate a revolutionary change in the quality of life of persons with sensory and/or motor deficits. Microelectrode technology represents the initial step towards this goal and has already improved the quality of life of many patients, as is evident from the success of auditory prostheses. Much effort has been invested in the development of miniaturized silicon (Si) microelectrodes, which allows one to analyze how individual neurons function by potentially recording single-units from them. However, when these devices are implanted into brain tissue for long-term recording, they quickly (days) lose electrical connectivity. We propose two-component coatings to improve the recording stability of Si-electrode arrays in the brain-component 1 is a neuro-adhesive layer on Si; and component B is the incorporation of sustained release vehicles within component 1. This strategy enables us to promote the integration of silicon electrodes with the brain with coatings that will enhance neuronal cell attachment (therefore increasing the proximity of neurons to the recording contact) and enhance their survival and at the same time decrease any inflammatory response due to implantation procedure or Si chemistry (by sustained, local release of neurotrophic factor BDNF and anti-inflammatory anti-sense ODNs directed against NFkB mRNA). In addition, we propose to use two novel, non-invasive optical imaging techniques to assess the success of our coatings in live animals to complement conventional immuno-histochemistry and histology. The conventional techniques require one to physically remove the electrode arrays before being analyzed (because Si is a very hard substrate and difficult to section histologically), and the novel optical imaging and histology techniques we propose will be a significant advance in studying the electrode-brain interface non-invasively to enable optimization of coating composition. Studies are proposed to thoroughly characterize our coatings in vitro (physical properties and for biocompatibility); implant a number of coating compositions in vivo in a rodent model to optimize for coatings with the least inflammatory response; and finally implant the best coating into primate cortex and compare recording stability to that obtained in our earlier experiments with the similar uncoated electrode arrays.